Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals

Fenzl, Anna; Itariu, Bianca; Kosi, Lana; Fritzer‐Szekeres, Monika; Kautzky‐Willer, Alexandra; Stulnig, Thomas M.; Kiefer, Florian W.

doi:10.1007/s00125-014-3208-x

Cited by 160 publications

(233 citation statements)

References 11 publications

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“…Nevertheless, our findings did not accord with a recent study performed by Fenzl et al (15) in which serum betatrophin was found to be not elevated in patients with T2DM. The disparities may be due to the difference in sample sizes, oral hypoglycemic agents, and different disease duration of T2DM.…”

Section: Discussioncontrasting

confidence: 99%

Increased Circulating Levels of Betatrophin in Newly Diagnosed Type 2 Diabetic Patients

et al. 2014

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OBJECTIVEBetatrophin, a newly identified hormone, has been recently characterized as a potent stimulator that increases the production and expansion of insulin-secreting b-cells in mice, but the physiological role of betatrophin remains poorly understood. This study measured for the first time serum betatrophin levels in newly diagnosed patients with type 2 diabetes (T2DM) and explored the correlations between its serum levels and various metabolic parameters in T2DM. RESEARCH DESIGN AND METHODSWe analyzed the concentrations of betatrophin by ELISA in blood samples of 166 well-characterized individuals in whom anthropometric parameters, oral glucose tolerance test (OGTT), glycosylated hemoglobin, blood lipids, insulin sensitivity (1/homeostasis model assesment of insulin resistance [1/HOMA-IR] and Matsuda index [ISI M ]), and insulin secretion were measured. The participants were divided into newly diagnosed T2DM patients (n = 83) and age-, sex-and BMI-matched healthy control subjects (n = 83). RESULTSSerum betatrophin levels were significantly higher in T2DM patients than in healthy control subjects (613.08 [422.19-813.08] vs. 296.57 [196.53-509.46] pg/mL; P < 0.01). Serum betatrophin positively correlated with age, 2-h post-OGTT glucose (2hPG), and postprandial serum insulin (PSI), but negatively with 1/HOMA-IR and ISI M in T2DM patients. In the control group, betatrophin was only positively associated with age. In T2DM subjects, multivariate regression analyses showed that age, 2hPG, and PSI were independent factors influencing serum betatrophin levels. CONCLUSIONSCirculating concentrations of betatrophin are significantly increased in T2DM patients. Our results suggest that betatrophin may play a role in the pathogenesis of T2DM.Precise regulation of b-cell function is crucial for maintaining blood glucose homeostasis (1). In type 2 diabetes (T2DM), ambient insulin resistance forces b-cells to produce more insulin, which ultimately results in exhaustion of insulin production secondary to deterioration of b-cell functions. Unfortunately, neither pharmacotherapy nor insulin injections can reverse ongoing failure of b-cell function to prevent uncontrolled hyperglycemia and the devastating microvascular, neurologic, and macrovascular complications of diabetes. Treatments that replenish b-cell

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Section: Discussioncontrasting

confidence: 99%

Increased Circulating Levels of Betatrophin in Newly Diagnosed Type 2 Diabetic Patients

et al. 2014

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“…Even after adjustment for age and duration of Type 2 diabetes, the correlation between betatrophin and increments of C‐peptide concentration was still statistically significant, which suggests that insulin secretion deficiency is one of the factors that regulate betatrophin concentrations in humans. In contrast to previous results 7, 9, 10, we did not find a relationship between circulating betatrophin concentrations and BMI, HbA 1c or levels of blood lipids such as triglycerides and HDL cholesterol.…”

Section: Discussioncontrasting

confidence: 99%

“…Previous reports have shown that age affects circulating betatrophin concentrations 7, 8, 9. In the present study, we found that betatrophin concentrations inversely correlated with the duration of Type 2 diabetes.…”

Section: Discussionsupporting

confidence: 73%

Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests

et al. 2015

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AimTo investigate the relationship between plasma betatrophin concentrations and insulin secretion capacity in people with Type 2 diabetes.MethodsGlucagon stimulation tests (1 mg) were performed in 70 people with Type 2 diabetes after an overnight fast. Plasma betatrophin concentrations were measured using an enzyme‐linked immunosorbent assay. Insulin secretion capacity was evaluated by measuring increments of C‐peptide concentration in response to glucagon stimulation, and creatinine clearance was determined by comparing creatinine concentrations in serum and 24‐h urine samples.ResultsPlasma betatrophin concentrations were positively correlated with duration of Type 2 diabetes (r = 0.34, P = 0.003), and negatively correlated with increments of C‐peptide concentration (r = 0.37, P = 0.001) and creatinine clearance (r = 0.37, P = 0.001). The correlation with increments of C‐peptide concentration remained significant after adjustment for age and duration of Type 2 diabetes (r = 0.25, P = 0.037). Multivariate analysis identified age and increments of C‐peptide concentration as independent factors associated with plasma betatrophin levels.ConclusionPlasma betatrophin levels inversely correlate with insulin secretion capacity, suggesting that betatrophin levels are regulated by insulin secretion capacity in humans.

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“…Interestingly, serum levels of this b cell effector are doubled in patients with type 1 diabetes mellitus (T1DM) as compared to age-matched healthy controls in a very recent study (6). Furthermore, Fenzl et al (7) demonstrated that the novel adipokine/hepatokine correlates significantly with an atherogenic lipid profile in small cohorts comprising of patients with morbid obesity or T2DM.…”

Section: Introductionmentioning

confidence: 98%

“…However, data on betatrophin regulation in humans so far is limited to patients with T1DM (6), morbid obesity (8), or T2DM (7,8,9), and there are no studies investigating betatrophin in GDM. Since betatrophin could potentially counteract impaired glucose control seen in GDM by improving b cell proliferation (5), our rationale was to investigate this novel adipokine/ hepatokine and its potential associations with other metabolic markers in human GDM.…”

Section: Introductionmentioning

confidence: 99%

Betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls

Ebert¹,

Kralisch²,

Wurst³

et al. 2015

European Journal of Endocrinology

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Objective: Betatrophin has recently been introduced as a novel adipokine/hepatokine, which promotes pancreatic b cell proliferation and improves glucose tolerance in several mouse models of insulin resistance. However, regulation of betatrophin in gestational diabetes mellitus (GDM), as well as its association with markers of obesity, such as glucose and lipid metabolism, inflammation, and renal function, have not been elucidated. Design and methods: Circulating betatrophin was quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by ELISA. In a subset of the study population comprising of 85 patients (41 previous controls, 44 previous women with GDM), postpartum betatrophin levels were measured in a follow-up study. Results: Median (interquartile range) serum betatrophin levels were higher in women with GDM (1.79 (0.53) mg/l) as compared to non-diabetic pregnant controls (1.58 (0.44) mg/l) (PZ0.002). In multivariate analysis, GDM status was an independent and positive predictor of circulating betatrophin (PZ0.001). Furthermore, betatrophin levels were significantly higher during gestation (1.70 (0.53) mg/l) as compared to postpartum levels (1.55 (0.66) mg/l) (PZ0.028). Moreover, postpartum irisin remained a positive and independent predictor of postpartum betatrophin concentrations. Conclusions: Women with GDM have significantly higher betatrophin levels as compared to healthy pregnant controls and GDM status positively predicts circulating betatrophin. Furthermore, postpartum levels are significantly lower as compared to betatrophin concentrations during pregnancy. Moreover, irisin is a significant predictor of postpartum betatrophin levels.

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Circulating betatrophin correlates with atherogenic lipid profiles but not with glucose and insulin levels in insulin-resistant individuals

Cited by 160 publications

References 11 publications

Increased Circulating Levels of Betatrophin in Newly Diagnosed Type 2 Diabetic Patients

Increased Circulating Levels of Betatrophin in Newly Diagnosed Type 2 Diabetic Patients

Correlation of circulating betatrophin concentrations with insulin secretion capacity, evaluated by glucagon stimulation tests

Betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls

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